Dosing and uses of Aptivus (tipranavir)
Adult dosage forms and strengths
capsule
- 250mg
oral solution
- 100mg/mL
HIV Infection
500 mg PO q12hr; coadministration with ritonavir 200 mg PO q12hr is required (boosted therapy)
Administration with ritonavir essential to achieve correct dosing and adequate blood levels
Renal Impairment
Dose adjustment not necessary
Hepatic Impairment
Mild (Child-Pugh class A): Dose adjustment not necessary
Moderate-to-severe (Child-Pugh class B or C): Concurrent use contraindicated
Pediatric dosage forms and strengths
capsule
- 250mg
oral solution
- 100mg/mL
HIV Infection
Neonates and infants: Safety and efficacy not established
>2 years: 14 mg/kg (tipranavir) coadministered with 6 mg/kg (ritonavir) PO q12hr, Or
375 mg/m² (tipranavir) coadministered with 150 mg/m² (ritonavir) PO q12hr
Do not exceed adult dose of 500 mg (tipranavir) coadministered with 200 mg (ritonavir) PO q12hr
Administration with ritonavir essential to achieve correct dosing and adequate blood levels
Dose reduction
- May reduce dose if not tolerated if patient does not have virus resistant to more than one PI
- 12 mg/kg (tipranavir) coadministered with 5 mg/kg (ritonavir) PO q12hr, OR
- 290 mg/m² (tipranavir) coadministered with 115 mg/m² (ritonavir) PO q12hr
Aptivus (tipranavir) adverse (side) effects
>10%
Diarrhea (15%)
Rash (3-21%)
Hypertriglyceridemia (61%)
Increased transaminases (26-32%)
1-10%
Abdominal pain (4%)
Dyspnea (2%)
Epistaxis (4%)
Dehydration (2%)
Fatigue (6%)
Headache (5%)
Weight loss (3%)
Nausea (5-9%)
Pyrexia (6%)
Anemia (3%)
Vomiting (6%)
Myalgia (2%)
<1%
Dizziness
Hepatitis
Decreased apetite
Flu-like syndrome
Hyperbilirubinemia
Insomnia
Increased lipase
Warnings
Black box warnings
Hepatitis and hepatic decompensation, including some fatalities, reported; extra vigilance warranted with chronic hepatitis B or hepatitis C coinfection because of increased risk of hepatotoxicity
Intracranial hemorrhage, both fatal and nonfatal, reported
Contraindications
Hypersensitivity
Moderate-severe hepatic impairment (Child-Pugh Class B & C)
Drugs that are contraindicated with tipranavir (when coadministered 'boosted' with ritonavir) include alpha1-adrenoreptor agonists (eg, alfuzosin), antiarrhythmics (amiodarone, bepridil, flecainide, propafenone, quinidine), rifampin, voriconazole, ergot derivatives (dihydroergotamine, ergonovine, ergotamine, methylergonovine), cisapride, St. John’s wort, lovastatin, simvastatin, lurasidone, pimozide, sildenafil (when used for PAH), midazolam, and triazolam
Cautions
Caution in mild hepatic impairment
Risk of severe, potentially fatal hepatotoxicity
Not recommended in treatment-naive patients
May have antiplatelet/anticoagulant action
Risk of potentially fatal intracranial hemorrhage
Risk of immune reconstitution syndrome if used in combination with other antiretroviral drugs
Fat redistribution with "cushingoid appearance" and "buffalo hump" may occur
Autoimmune disorders (such as Graves’ disease, polymyositis, and Guillain-Barré syndrome) have also been reported to occur in the setting of immune reconstitution; however, the time to onset is more variable, and can occur many months after initiation of treatment
Must be coadministered with ritonavir
Sulfonamide allergy
Coadministration with other CYP3A4 substrates (ritonavir inhibits CYP3A4 and increases toxicity risk for drugs metabolized by CYP3A4)
Increased risk of rash, especially with hormonal contraceptives
Risk of large increase in total cholesterol and triglycerides
Contains 116 IU/mL vitamin E (>RDA); limit supplemented vitamin e
Pregnancy and lactation
Pregnancy category: C
Lactation: do not nurse (HIV-infected mothers shouldn't nurse anyway)
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Aptivus (tipranavir)
Mechanism of action
Protease Inhibitor; inhibits cleavage of Gag-Pol polyprotein precursors, which in turn causes the formation of immature, noninfectious viral particles.
Pharmacokinetics
Bioavailability: Increased by food
Protein Bound: 99.9%
Vd: 7.7-10 L
Half-Life: 5.5-6 hr
Metabolism: primarily by liver CYP3A4
Excretion: Feces (82.3% ); urine (4%)
Peak plasma time: 3 hr
Administration
Oral Administration
If taken with ritonavir tablets: Take with food
If taken with ritonavir capsules and oral solution: Take with food if possible (may improve tolerability)
